scholarly journals The Steroidogenic Acute Regulatory Protein Is Expressed in Steroidogenic Cells of the Day-Old Brain

Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4775-4780 ◽  
Author(s):  
Steven R. King ◽  
Stephen D. Ginsberg ◽  
Tomohiro Ishii ◽  
Roy G. Smith ◽  
Keith L. Parker ◽  
...  
Keyword(s):  
De Novo ◽  
Metastatic Lymph Node ◽  
Regulatory Protein ◽  
Cell Types ◽  
Adult Brain ◽  
Peripheral Tissues ◽  
Cytochrome P450scc ◽  
Star Protein ◽  
Steroidogenic Acute Regulatory ◽  
The Brain

Abstract Although recent research has focused on the fundamental role(s) of steroids synthesized de novo in the brain on development, the mechanism by which production of these neurosteroids is regulated remains unclear. Steroid production in peripheral tissues is acutely regulated by the steroidogenic acute regulatory (StAR) protein, which mediates the rate-limiting step in steroid biosynthesis: the intramitochondrial delivery of cholesterol to cytochrome P450scc for conversion to steroid. We recently demonstrated that StAR is present in discrete cell types in the adult brain, suggesting that neurosteroid production is mediated by StAR. Nevertheless, little is known regarding the presence of StAR in the developing brain. In the present study, the presence of StAR and for the first time, its homolog, the putative cholesterol transport protein metastatic lymph node 64 (MLN64), were defined in the neonatal mouse brain using immunocytochemical techniques. Both StAR and MLN64 were found to be present in the brain with staining patterns characteristic to each protein, indicating the authenticity of StAR and MLN64 immunoreactivity. Furthermore, we found MLN64 to be expressed in the adult brain as well, apparently at higher levels than StAR. Importantly, StAR protein is present in cells that also express P450scc. These data suggest that, as with the adult, neurosteroid production during development occurs through a StAR-mediated pathway.

scholarly journals Establishment of a Human Nonluteinized Granulosa Cell Line that Transitions from the Gonadotropin-Independent to the Gonadotropin-Dependent Status

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2851-2860 ◽  
Author(s):  
Bayasula ◽  
Akira Iwase ◽  
Tohru Kiyono ◽  
Sachiko Takikawa ◽  
Maki Goto ◽  
...  
Keyword(s):  
Cell Line ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Early Stage ◽  
Regulatory Protein ◽  
Cell Types ◽  
Mrna Levels ◽  
Steroidogenic Cell ◽  
Morphogenetic Protein ◽  
Steroidogenic Acute Regulatory

The ovary is a complex endocrine organ responsible for steroidogenesis and folliculogenesis. Follicles consist of oocytes and two primary steroidogenic cell types, the granulosa cells, and the theca cells. Immortalized human granulosa cells are essential for researching the mechanism of steroidogenesis and folliculogenesis. We obtained granulosa cells from a 35-yr-old female and immortalized them by lentivirus-mediated transfer of several genes so as to establish a human nonluteinized granulosa cell line (HGrC1). We subsequently characterized HGrC1 and investigated its steroidogenic performance. HGrC1 expressed enzymes related to steroidogenesis, such as steroidogenic acute regulatory protein, CYP11A, aromatase, and gonadotropin receptors. Stimulation with FSH increased the mRNA levels of aromatase, which consequently induced the aromatization of androstenedione to estradiol. Activin A increased the mRNA levels of the FSH receptor, which were synergistically up-regulated with FSH stimulation. HGrC1 also expressed a series of ligands and receptors belonging to the TGF-β superfamily. A Western blot analysis showed that bone morphogenetic protein (BMP)-4, BMP-6, and BMP-7 phosphorylated small mother against decapentaplegic (Smad)1/5/8, whereas growth differentiation factor-9 phosphorylated Smad2/3. BMP-15 and anti-Müllerian hormone phosphorylated Smad1/5/8 while also weakly phosphorylating Smad2/3. These results indicate that HGrC1 may possess the characteristics of granulosa cells belonging to follicles in the early stage. HGrC1 might also be capable of displaying the growth transition from a gonadotropin-independent status to gonadotropin-dependent one.

scholarly journals The potential function of steroid sulphatase activity in steroid production and steroidogenic acute regulatory protein expression

2004 ◽  
Vol 380 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Teruo SUGAWARA ◽  
Seiichiro FUJIMOTO
Keyword(s):  
Western Blot ◽  
Blot Analysis ◽  
Expression Vector ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Steroid Production ◽  
Star Protein ◽  
Protein Levels ◽  
Steroid Sulphatase ◽  
Steroidogenic Acute Regulatory

The first step in the biosynthesis of steroid hormones is conversion of cholesterol into pregnenolone. StAR (steroidogenic acute regulatory) protein plays a crucial role in the intra-mitochondrial movement of cholesterol. STS (steroid sulphatase), which is present ubiquitously in mammalian tissues, including the placenta, adrenal gland, testis and ovary, desulphates a number of 3β-hydroxysteroid sulphates, including cholesterol sulphate. The present study was designed to examine the effect of STS on StAR protein synthesis and steroidogenesis in cells. Steroidogenic activities of COS-1 cells that had been co-transfected with a vector for the cholesterol P450scc (cytochrome P450 side-chain-cleavage enzyme) system, named F2, a StAR expression vector (pStAR), and an STS expression vector (pSTS) were assayed. Whole-cell extracts were subjected to SDS/PAGE and then to Western blot analysis. pSTS co-expressed in COS-1 cells with F2 and pStAR increased pregnenolone synthesis 2-fold compared with that of co-expression with F2 and pStAR. Western blot analysis using COS-1 cells that had been co-transfected with pSTS, F2 and pStAR revealed that StAR protein levels increased, whereas STS and P450scc protein levels did not change. The amount of StAR protein translation products increased when pSTS was added to an in vitro transcription–translation reaction mixture. Pulse–chase experiments demonstrated that the 37 kDa StAR pre-protein disappeared significantly (P<0.01) more slowly in COS-1 cells that had been transfected with pSTS than in COS-1 cells that had not been transfected with pSTS. The increase in StAR protein level is not a result of an increase in StAR gene expression, but is a result of both an increase in translation and a longer half-life of the 37 kDa pre-StAR protein. In conclusion, STS increases StAR protein expression level and stimulates steroid production.

scholarly journals In vivo effects of adrenocorticotrophin on the expression of the hamster steroidogenic acute regulatory protein

1998 ◽  
Vol 21 (2) ◽  
pp. 131-139 ◽  
Author(s):  
A Fleury ◽  
L Ducharme ◽  
JG LeHoux
Keyword(s):  
Untranslated Region ◽  
Regulatory Protein ◽  
Northern Blotting ◽  
Polyadenylation Signal ◽  
Amino Acid Residues ◽  
Star Protein ◽  
Blotting Analysis ◽  
Steroidogenic Acute Regulatory ◽  
In Vivo Effects

In this study, we report the cDNA cloning of hamster adrenal steroidogenic acute regulatory (StAR) protein and the effect of adrenocorticotrophin (ACTH) on its expression in vivo. A hamster adrenal cDNA library was screened using an 852 bp fragment obtained by polymerase chain reaction; this fragment corresponds to the entire coding sequence (CDS) of the hamster adrenal StAR cDNA. Ten clones of different lengths were isolated and sequenced. The longest clone was 1564 bp and contained 34 bp in the 5'-untranslated region, 852 bp in the CDS, and 678 bp in the 3'-untranslated region (3'-UTR). Two polyadenylation signal sequences were found in the 3'-UTR. The CDS of the ten isolated clones was identical, but six of these lacked the last 132 nucleotides in the 3'-UTR, thus indicating that they had used the first polyadenylation signal. The hamster StAR protein contains 284 amino acid residues, and is 91.9% homologous to mouse, 90.5% to rat, 86.4% to human, 85% to porcine, and 82.5% to bovine StAR protein. Southern blot analysis indicated the presence of only one StAR gene in the hamster genome. Northern blotting analysis revealed the presence of the StAR mRNA in male and female steroidogenic tissues, namely adrenals and gonads, but not in the liver or in the kidneys of either sex. Three mRNA species of 1.7, 3.1 and 5.3 kb were found in whole hamster adrenals. Administration of ACTH to hamsters provoked increases (two- to threefold) in the adrenal content of the StAR mRNA within 1 h in vivo. Western blotting analysis on adrenal mitochondria showed that the level of StAR protein was also significantly elevated (1.5-fold) 1 h after ACTH treatment.

scholarly journals A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Nathan G Skene ◽  
Marcia Roy ◽  
Seth GN Grant
Keyword(s):  
Young Adults ◽  
Age Of Onset ◽  
Cell Types ◽  
Adult Brain ◽  
Molecular Organization ◽  
Tissue Samples ◽  
Genetic Mechanisms ◽  
Gene Regulatory ◽  
The Brain ◽  
Schizophrenia Susceptibility

The genetic mechanisms regulating the brain and behaviour across the lifespan are poorly understood. We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression changes in neuronal, glial and endothelial cell-types, which enabled prediction of age from tissue samples. A major lifespan landmark was the peak change in trajectories occurring in humans at 26 years and in mice at 5 months of age. This species-conserved peak was delayed in females and marked a reorganization of expression of synaptic and schizophrenia-susceptibility genes. The lifespan calendar predicted the characteristic age of onset in young adults and sex differences in schizophrenia. We propose a genomic program generates a lifespan calendar of gene regulation that times age-dependent molecular organization of the brain and mutations that interrupt the program in young adults cause schizophrenia.

scholarly journals Interleukin-1alpha stimulates steroidogenic acute regulatory protein expression via p38 MAP kinase in immature rat Leydig cells

2003 ◽  
Vol 30 (1) ◽  
pp. 59-67 ◽  
Author(s):  
K Svechnikov ◽  
DM Stocco ◽  
O Soder
Keyword(s):  
Protein Expression ◽  
Map Kinase ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Regulatory Protein ◽  
P38 Map Kinase ◽  
Dependent Manner ◽  
Star Protein ◽  
Adult Leydig Cells ◽  
Steroidogenic Acute Regulatory

We have investigated the involvement of the steroidogenic acute regulatory (StAR) protein in interleukin-1alpha (IL-1alpha)-induced steroidogenesis in immature (40-day-old) and adult Leydig cells in vitro. Further, IL-1alpha-mediated signaling pathway(s) controlling StAR expression in immature Leydig cells were also studied. IL-1alpha stimulated both androgen production and StAR protein expression in a dose- and time-dependent manner in immature but not adult Leydig cells. These effects of IL-1alpha were prevented by pretreatment of the cells with the specific inhibitors of the p38 MAP kinase, SB203580 and PD169316, suggesting that this kinase is an important part of IL-1alpha signaling in the immature Leydig cell. The present results suggest that IL-1alpha, which is constitutively produced by the rat testis from postnatal day 25, is an important paracrine regulator of postnatal Leydig cell maturation. Regulation of StAR protein expression is one of the possible mechanisms by which IL-1alpha contributes to the differentiation of immature Leydig cells into adult cells.

scholarly journals Diametric Effects of Bacterial Endotoxin Lipopolysaccharide on Adrenal and Leydig Cell Steroidogenic Acute Regulatory Protein

Endocrinology ◽  
2000 ◽  
Vol 141 (11) ◽  
pp. 4000-4012 ◽  
Author(s):  
Karen Held Hales ◽  
Thorsten Diemer ◽  
Salil Ginde ◽  
Birinder K. Shankar ◽  
Maretha Roberts ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Leydig Cells ◽  
Regulatory Protein ◽  
Serum Testosterone ◽  
Northern Analysis ◽  
Dependent Manner ◽  
Star Protein ◽  
Adrenal Steroidogenesis ◽  
Serum Lh ◽  
Steroidogenic Acute Regulatory

Abstract Immune activation results in the activation of adrenal steroidogenesis and inhibition of gonadal steroidogenesis. Previous studies indicated that these effects were caused primarily by activation and suppression of the secretion of ACTH and LH, respectively. However, other evidence indicated a direct effect of the immune system on the gonads. In this study, serum testosterone, quantitated by RIA after lipopolysaccharide injection, showed a significant decrease within 2 h. Parallel measurement of serum LH showed no change. There were no differences in LH receptor or cAMP produced in Leydig cells between vehicle- and lipopolysaccharide-injected mice. The 30-kDa form of the steroidogenic acute regulatory (StAR) protein was quantitated, by Western blot, in Leydig cells and was found to decrease in a time-dependent manner. No change in StAR protein messenger RNA (mRNA) was detected by Northern analysis during this time, nor were any changes found in the levels of mRNA for the steroidogenic enzymes P450scc, 3β-hydroxysteroid dehydrogenaseΔ 4-Δ5-isomerase, or P450c17. In the adrenal, StAR protein was increased, as was StAR protein mRNA. No changes were observed in the levels of mRNA for P450scc, 3β-hydroxysteroid dehydrogenaseΔ 4-Δ5-isomerase, or P450c21. Thus, although the mechanisms of regulation differ, changes in the levels of StAR protein are a sensitive indicator of the steroidogenic capacity of these two tissues.

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